The mechanisms of tolerance and immune induction in hapten-carrier model systems will be studied using fluoresceinated antigens and hapten-specific lymphocyte purification to isolate specific cells which bind antigen. The cell surface and molecular changes in these cells will be analyzed, including the roles of IgD and IgM isotypes, mitogen receptors, and other cell surface markers. The use of monoclonal reagents in altering states of responsiveness will be detailed. We will determine the susceptibility of B cell subpopulations (responsive to different forms of the same hapten) from neonatal and adult mice to triggering and tolerance. In addition, lymphocyte clones will be established, using somatic cell hybridization of isolated hapten-specific lymphoid cells, direct agar cloning and viral transformation. We will emphasize cell culture and B cell cloning technologies for the molecular analysis of triggering and tolerance. Finally, studies of T cell tolerance at the mature helper cell and at the precursor level will be continued using carrier tolerance as a model.